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Tribbles homolog 2 inactivates C/EBPα and causes acute myelogenous leukemia
被引:212
作者:

Keeshan, Karen
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

He, Yiping
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Wouters, Bas J.
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Shestova, Olga
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Xu, Lanwei
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Sai, Hong
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Rodriguez, Carlos G.
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Maillard, Ivan
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Tobias, John W.
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Valk, Peter
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Carroll, Martin
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Aster, Jon C.
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Delwel, Ruud
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机构: Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

Pear, Warren S.
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Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
机构:
[1] Univ Penn, Inst Med & Engn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Erasmus MC, Dept Hematol, NL-3015 GE Rotterdam, Netherlands
[3] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA
[4] Univ Penn Bioinformat Core, Philadelphia, PA 19104 USA
[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
来源:
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D O I:
10.1016/j.ccr.2006.09.012
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Tribbles homolog 2 (Trib2) was identified as a downregulated transcript in leukemic cells undergoing growth arrest. To investigate the effects of Trib2 in hematopoietic progenitors, mice were reconstituted with hematopoietic stem cells retro-virally expressing Trib2. Trib2-transduced bone marrow cells exhibited a growth advantage ex vivo and readily established factor-dependent cell lines. In vivo, Trib2-reconstituted mice uniformly developed fatal transplantable acute myelogenous leukemia (AML). In mechanistic studies, we found that Trib2 associated with and inhibited C/EBP alpha. Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBP alpha.
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页码:401 / 411
页数:11
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